Grisar T, Guillaume D, Delgado-Escueta A V
Laboratory of Comparative and General Biochemistry, University of Liege, Belgium.
Epilepsy Res. 1992 Jul;12(2):141-9. doi: 10.1016/0920-1211(92)90034-q.
The authors review some of their experimental data on the contribution of Na(+)- and K(+)-dependent adenosine triphosphatase (Na+,K(+)-ATPase) to focal epilepsy. It has been previously demonstrated that high extracellular K+ concentration increases glial Na+,K(+)-ATPase specific activities in normal conditions while this was not observed in neuronal preparations. At this time, it was hypothesized that this molecular mechanism could play a role in removing K+ released in the extracellular space during neuronal firing. These results have therefore been investigated in acute and chronic epileptogenic lesions of cats with freeze lesion. It was demonstrated that within the primary (F) and the secondary or 'mirror' (M) focus the K+ activation of the glial Na+,K(+)-ATPase dramatically decreased compared to both control animals (C) and the perifocal (PF) non epileptogenic area. Similar results were observed in man when using specimens of anterolateral temporal neocortex obtained during temporal lobectomies in patients with intractable temporal lobe epilepsy, compared with postmortem human specimens or control brain tissues. The modifications of the level of phosphorylation of partially purified Na+,K(+)-ATPase was also investigated in the epileptic cortex in these two experimental conditions. The catalytic subunits were resolved by sodium dodecylsulfate (SDS) gel electrophoresis and their phosphorylation levels were measured in the presence of various concentrations of K+ ions which dephosphorylate the catalytic subunit. K(+)-induced dephosphorylation was decreased in primary and secondary foci of acutely lesioned cats. Those alterations, due to a decreased affinity for K+, were limited to the alpha (-) subunit. In cats with chronic lesions, the dephosphorylating step of the Na+,K+-ATPase catalytic subunit recovered to normal affinity for K+.(ABSTRACT TRUNCATED AT 250 WORDS)
